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Abstract
Cancer stem cells (CSCs) are thought to sustain cancer progression, metastasis and recurrence after therapy. There is in vitro and in vivo evidence supporting the idea that CSCs are highly chemoresistant. Epigenetic gene regulation is crucial for both stem cell biology and chemoresistance. In this review, we summarize current data on epigenetic mechanisms of chemoresistance in cancer stem cells. We propose a model integrating classical CSC pathways (Wnt, Hedgehog and Notch), epigenetic effectors (Polycomb) and drug resistance genes (ABCG2, CD44). Moreover, we analyze the potential of epigenetic drugs to reverse CSC chemoresistance. In the future, CSC epigenomic profiling could help to dissect specific chemoresistance pathways, and have a significant clinical impact for patient stratification and rational design of therapeutic regimens.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.